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Lund University Lund University Publications2000-01-01T00:00+00:001dailyCerebrospinal Fluid Biomarker Levels as Markers for Nursing Home Placement and Survival Time in Alzheimer's Disease
https://lup.lub.lu.se/search/publication/9165161f-5d72-4a1f-8856-2e75c274926a
Wattmo, CarinaBlennow, KajHansson, Oskar2021BACKGROUND: Cerebrospinal fluid (CSF) biomarkers are associated with conversion from mild cognitive impairment to Alzheimer's disease (AD), but their predictive value for later end-points has been less evaluated with inconsistent results.OBJECTIVE: We investigated potential relationships between CSF amyloid-β1-42 (Aβ42), phosphorylated tau (P-tau), and total tau (T-tau) with time to nursing home placement (NHP) and life expectancy after diagnosis.METHODS: This prospective observational study included 129 outpatients clinically diagnosed with mild-to-moderate AD who underwent a lumbar puncture. The CSF biomarkers were analysed with xMAP technology. Dates of institutionalisation and death were recorded.RESULTS: After 20 years of follow-up, 123 patients (95%) were deceased. The participants with abnormal P-tau and T-tau (A+ T+ (N)+) died earlier than those with normal P-tau/abnormal T-tau (A+ T- (N)+) (mean, 80.5 vs. 85.4 years). Linear associations were demonstrated between lower Aβ42 and shorter time to NHP (p = 0.017), and higher P-tau and younger age at death (p = 0.016). No correlations were detected between survival after AD diagnosis and CSF biomarkers. In sex- and-age-adjusted Cox regression models, higher P-tau and T-tau were independent predictors of shorter lifespan after diagnosis. In multivariate Cox models, older age and lower baseline cognitive status, but not elevated tau, significantly precipitated both institutionalisation and death.CONCLUSION: These findings suggest that CSF biomarker levels plateau in the dementia phase of AD, which may limit their possible relationships with clinical end-points, such as NHP and survival time. However, the biomarkers reflect the central pathophysiologies of AD. In particular, pathologic tau is associated with more advanced disease, younger age at onset, and earlier death.application/pdfhttps://lup.lub.lu.se/record/9165161f-5d72-4a1f-8856-2e75c274926ahttp://dx.doi.org/10.2174/1567205018666211022164952https://lup.lub.lu.se/search/files/110315068/Wattmo_CSF_biomarkers_NHP_survival.pdfpmid:34719365scopus:85122546321enginfo:eu-repo/semantics/openAccessCurrent Alzheimer Research; 18(7), pp 573-584 (2021)ISSN: 1875-5828NeurologyCerebrospinal Fluid Biomarker Levels as Markers for Nursing Home Placement and Survival Time in Alzheimer's Diseasecontributiontojournal/articleinfo:eu-repo/semantics/articletextAtrial Fibrillation and Dementia : A Report From the AF-SCREEN International Collaboration
https://lup.lub.lu.se/search/publication/2e076f08-56a2-44e5-87e0-a054dc343ac2
Rivard, LénaFriberg, LeifConen, DavidHealey, Jeffrey S.Berge, TrygveBoriani, GiuseppeBrandes, AxelCalkins, HughCamm, A. JohnYee Chen, LinLluis Clua Espuny, JosepCollins, RonanConnolly, StuartDagres, NikolaosElkind, Mitchell S.V.Engdahl, JohanField, Thalia S.Gersh, Bernard J.Glotzer, Taya V.Hankey, Graeme J.Harbison, Joseph A.Georg Haeusler, KarlHills, Mellanie T.Johnson, Linda S.B.Joung, BoyoungKhairy, PaulKirchhof, PaulusKrieger, DerkLip, Gregory Y.H.Løchen, Maja LisaMadhavan, MaliniMairesse, Georges H.Montaner, JoanNtaios, GeorgeQuinn, Terence J.Rienstra, MichielRosenqvist, MårtenSandhu, Roopinder K.Smyth, BredaSchnabel, Renate B.Stavrakis, StavrosThemistoclakis, SakisVan Gelder, Isabelle C.Wang, Ji GuangFreedman, Ben2022-02Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.https://lup.lub.lu.se/record/2e076f08-56a2-44e5-87e0-a054dc343ac2http://dx.doi.org/10.1161/CIRCULATIONAHA.121.055018pmid:35100023scopus:85123974674engCirculation; 145(5), pp 392-409 (2022)ISSN: 1524-4539Cardiac and Cardiovascular SystemsNeurologyatrial fibrillationcognitive dysfunctiondementiaAtrial Fibrillation and Dementia : A Report From the AF-SCREEN International Collaborationcontributiontojournal/systematicreviewinfo:eu-repo/semantics/articletextCortical microvascular raspberries and ageing : an independent but not exclusive relationship
https://lup.lub.lu.se/search/publication/77ffd2fe-2c8c-4836-8518-39f79066d39a
Ek Olofsson, HenricÖsterling Delshammar, TheaEnglund, Elisabet2023-12Introduction: Raspberries are cerebral microvascular formations of unknown origin, defined as three or more transversally sectioned vascular lumina surrounded by a common perivascular space. We have previously demonstrated an increased raspberry density in the cortex of patients with vascular dementia and cerebral atherosclerosis, while studies by other authors on overlapping and synonymously defined vascular entities mainly associate them with advancing age. The aim of the present study was to examine the relationship between raspberries and age in a large study sample while including multiple potential confounding factors in the analysis.Materials and methods: Our study sample consisted of 263 individuals aged 20–97 years who had undergone a clinical autopsy including a neuropathological examination. The cortical raspberry density had either been quantified as part of a previous study or was examined de novo in a uniform manner on haematoxylin- and eosin-stained tissue sections from the frontal lobe. The medical records and autopsy reports were assessed regarding neurodegeneration, cerebral infarcts, cerebral atherosclerosis and small vessel disease, cardiac hypertrophy, nephrosclerosis, hypertension, and diabetes mellitus. With the patients grouped according to 10-year age interval, non-parametric tests (the Kruskal–Wallis test, followed by pairwise testing with Bonferroni-corrected P values) and multiple linear regression models (not corrected for multiple tests) were performed.Results: The average raspberry density increased with advancing age. The non-parametric tests demonstrated statistically significant differences in raspberry density when comparing the groups aged 60–99 years and 70–99 years to those aged 20–29 years (P < 0.012) and 30–59 years (P < 0.011), respectively. The multiple linear regression models demonstrated positive associations with age interval (P < 0.001), cerebral atherosclerosis (P = 0.024), cardiac hypertrophy (P = 0.021), hypertension subgrouped for organ damage (P = 0.006), and female sex (P = 0.004), and a tendency towards a negative association with Alzheimer’s disease neuropathologic change (P = 0.048).Conclusion: The raspberry density of the frontal cortex increases with advancing age, but our results also indicate associations with acquired pathologies. Awareness of the biological and pathological context where raspberries occur can guide further research on their origin.https://lup.lub.lu.se/record/77ffd2fe-2c8c-4836-8518-39f79066d39ahttp://dx.doi.org/10.1186/s40478-023-01700-zpmid:38087325scopus:85179344066engActa Neuropathologica Communications; 11, no 195 (2023)ISSN: 2051-5960NeurologyAgingAtherosclerosisBrain ischemiaCardiac hypertrophyCerebral angiogenesisCerebral neovascularizationCerebrovascular diseaseHypertensionSmall vessel diseaseCortical microvascular raspberries and ageing : an independent but not exclusive relationshipcontributiontojournal/articleinfo:eu-repo/semantics/articletext